pH-weighted molecular MRI in human traumatic brain injury (TBI) using amine proton chemical exchange saturation transfer echoplanar imaging (CEST EPI)

Cerebral acidosis is a consequence of secondary injury mechanisms following traumatic brain injury (TBI), including excitotoxicity and ischemia, with potentially significant clinical implications. However, there remains an unmet clinical need for technology for non-invasive, high resolution pH imaging of human TBI for studying metabolic changes following injury. The current study examined 17 patients with TBI and 20 healthy controls using amine chemical exchange saturation transfer echoplanar imaging (CEST EPI), a novel pH-weighted molecular MR imaging technique, on a clinical 3T MR scanner. Results showed significantly elevated pH-weighted image contrast (MTR(asym) at 3 ppm) in areas of T2 hyperintensity or edema (P < 0.0001), and a strong negative correlation with Glasgow Coma Scale (GCS) at the time of the MRI exam (R(2) = 0.4777, P = 0.0021), Glasgow Outcome Scale - Extended (GOSE) at 6 months from injury (R(2) = 0.5334, P = 0.0107), and a non-linear correlation with the time from injury to MRI exam (R(2) = 0.6317, P = 0.0004). This evidence suggests clinical feasibility and potential value of pH-weighted amine CEST EPI as a high-resolution imaging tool for identifying tissue most at risk for long-term damage due to cerebral acidosis.